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Articles by N Wu
Total Records ( 2 ) for N Wu
  N Wu , Y Zhao , Y Yin , Y Zhang and J. Luo
 

Our previous studies have demonstrated that bone morphogenetic protein 9 (BMP-9) is one of the most efficacious BMPs to induce osteoblast differentiation of mesenchymal stem cells (MSCs). However, the molecular mechanism underlying the BMP-9-induced osteogenic differentiation of MSCs remains to be fully elucidated. In this study, dominant negative (DN) type II TGF-β receptors were constructed and introduced into C3H10T1/2 stem cells, then in vitro and in vivo assays were carried out to analyze and identify the type II TGF-β receptors required for BMP-9-induced osteogenesis. We found that three DN type II TGF-β receptors, DN-BMPRII, DN-ActRII, and DN-ActRIIB, diminished BMP-9-induced alkaline phosphatase (ALP) activity, led to a decrease in BMP-9-induced Smad binding element (SBE)-controled reporter activity, reduced BMP-9-induced expressions of Smad6 and Smad7, and decreased BMP-9-induced mineralization in vitro and ectopic bone formation in vivo, finally resulted in decreased bone masses and immature osteogenesis. These findings strongly suggested that three wild-type II TGF-β receptors, BMPRII, ActRII and ActRIIB, may play a functional role in BMP-9-induced osteogenic differentiation of C3H10T1/2 cells. However, C3H10T1/2 stem cells can express BMPRII and ActRII, but not ActRIIB. Using RNA interference (RNAi), we found that luciferase reporter activity and ALP activity induced by BMP-9 were accordingly inhibited along with the knockdown of BMPRII and ActRII. Taken together, our results demonstrated that BMPRII and ActRII are the functional type II TGF-β receptors in BMP-9-induced osteogenic differentiation of C3H10T1/2 cells.

  N Wu , L Yin , E. A Hanniman , S Joshi and M. A. Lazar
 

Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erb tightly controls the level of its own ligand. Heme binding to Rev-erb recruits the NCoR/histone deacetylase 3 (HDAC3) corepressor complex to repress the transcription of the coactivator PGC-1, a potent inducer of heme synthesis. Depletion of Rev-erb derepresses PGC-1, resulting in increased heme levels. Conversely, increased Rev-erb reduces intracellular heme, and impairs mitochondrial respiration in a heme-dependent manner. Consistent with this bioenergetic impairment, overexpression of Rev-erb dramatically inhibits cell growth due to a cell cycle arrest. Thus, Rev-erb modulates the synthesis of its own ligand in a negative feedback pathway that maintains heme levels and regulates cellular energy metabolism.

 
 
 
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